Identification and characterization of cell type-specific and ubiquitous chromatin regulatory structures in the human genome.-猫眼课题宝

人类基因组中细胞类型特异性和无处不在调节结构的鉴定和表征。

DOI：

10.1371/journal.pgen.0030136

发表时间：

2007-08

期刊：

PLOS GENETICS

影响因子：

4.5

通讯作者：

中科院分区：

生物学2区

文献类型：

作者：

Xi, Hualin;Shulha, Hennady P.;Lin, Jane M.;Vales, Teresa R.;Fu, Yutao;Bodine, David M.;Mckay, Ronald D. G.;Chenoweth, Josh G.;Tesar, Paul J.;Furey, Terrence S.;Ren, Bing;Weng, Zhiping;Crawford, Gregory E.

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1950163/?report=classic

The identification of regulatory elements from different cell types is necessary for understanding the mechanisms controlling cell type–specific and housekeeping gene expression. Mapping DNaseI hypersensitive (HS) sites is an accurate method for identifying the location of functional regulatory elements. We used a high throughput method called DNase-chip to identify 3,904 DNaseI HS sites from six cell types across 1% of the human genome. A significant number (22%) of DNaseI HS sites from each cell type are ubiquitously present among all cell types studied. Surprisingly, nearly all of these ubiquitous DNaseI HS sites correspond to either promoters or insulator elements: 86% of them are located near annotated transcription start sites and 10% are bound by CTCF, a protein with known enhancer-blocking insulator activity. We also identified a large number of DNaseI HS sites that are cell type specific (only present in one cell type); these regions are enriched for enhancer elements and correlate with cell type–specific gene expression as well as cell type–specific histone modifications. Finally, we found that approximately 8% of the genome overlaps a DNaseI HS site in at least one the six cell lines studied, indicating that a significant percentage of the genome is potentially functional. There are many different types of gene regulatory elements that control gene expression. Identifying the location of these regulatory elements in the genome, as well as understanding how exactly they control gene expression in different cell types, has been a major challenge. Here, we use a relatively new strategy to identify all gene regulatory elements within a select 1% of the human genome from six diverse human cell types. We find that only 22% of gene regulatory elements are shared among all cell types studied. Among these, 86% are located near annotated transcription start sites and 10% are bound by CTCF, a protein with known enhancer-blocking insulator activity. The gene regulatory elements that are found to be cell type specific are highly correlated with cell type–specific gene expression as well as cell type–specific chromatin modifications. This indicates that we have made a significant step toward understanding why some genes are expressed in all different cell types within the human body, and why others are only expressed in certain cell types.